Deep transcranial magnetic stimulation for adolescents with treatment-resistant depression: A preliminary dose-finding study exploring safety and clinical effectiveness.

BACKGROUND: Transcranial magnetic stimulation (TMS) is an intervention for treatment-resistant depression (TRD) that modulates neural activity. Deep TMS (dTMS) can target not only cortical but also deeper limbic structures implicated in depression. Although TMS has demonstrated safety in adolescents, dTMS has yet to be applied to adolescent TRD. OBJECTIVE/HYPOTHESIS: This pilot study evaluated the safety, tolerability, and clinical effects of dTMS in adolescents with TRD. We hypothesized dTMS would be safe, tolerable, and efficacious for adolescent TRD. METHODS: 15 adolescents with TRD (Age, years: M = 16.4, SD = 1.42) completed a six-week daily dTMS protocol targeting the left dorsolateral prefrontal cortex (BrainsWay H1 coil, 30 sessions, 10 Hz, 3.6 s train duration, 20s inter-train interval, 55 trains; 1980 total pulses per session, 80 % to 120 % of motor threshold). Participants completed clinical, safety, and neurocognitive assessments before and after treatment. The primary outcome was depression symptom severity measured by the Children's Depression Rating Scale-Revised (CDRS-R). RESULTS: 14 out of 15 participants completed the dTMS treatments. One participant experienced a convulsive syncope; the other participants only experienced mild side effects (e.g., headaches). There were no serious adverse events and minimal to no change in cognitive performance. Depression symptom severity significantly improved pre- to post-treatment and decreased to a clinically significant degree after 10 treatment sessions. Six participants met criteria for treatment response. LIMITATIONS: Main limitations include a small sample size and open-label design. CONCLUSIONS: These findings provide preliminary evidence that dTMS may be tolerable and associated with clinical improvement in adolescent TRD.

Prevention starts here: effectiveness of substance abuse prevention module among adolescent students in Bengaluru - a quasi experimental study.

OBJECTIVES: This study aims to evaluate the effectiveness of a structured educational module on substance abuse prevention program among adolescents in enhancing their knowledge against substance abuse. METHODS: A quasi-experimental design was employed involving 120 students (mean age: 14.3±1.03 years, 59.2% boys) from two English medium schools. Participants were exposed to a structured module on substance abuse over a month. The study assessed changes in knowledge through pretest and post-test evaluations. Statistical analyses examined improvements in scores and the relationship between class of study and post-test knowledge scores. RESULTS: The intervention significantly improved students' knowledge about substance abuse (p<0.001) across all measured domains, genders, and classes, with the exception of the 7th class. A positive correlation was found between the class of study and post-test scores (Rs=0.288, p<0.001), indicating that higher classes were associated with greater improvements in knowledge. These findings suggest that the training effectively increased awareness and understanding of substance abuse among participants. CONCLUSIONS: The substance abuse prevention program successfully enhanced adolescents' knowledge and equipped them with resilience and coping strategies, thus reducing their vulnerability to peer pressure and substance abuse. Despite the lack of significant improvement in the 7th class, the overall positive outcomes underscore the importance of implementing such educational interventions to foster healthy development and well-being among students. Further research is encouraged to explore the specific barriers to effectiveness in younger classes and to refine program content accordingly.

Chemical Tailoring Assisted non-TADF to TADF Switching in Carbazole-Benzophenone Emitter - An In-silico Investigation.

Organic light-emitting diodes (OLEDs) have become one of the most popular lighting technologies since they offer several advantages over conventional devices. In carbazole-benzophenone (CzBP) OLED devices, the polymeric form of the compound is previously reported to be Thermally Activated Delayed Fluorescence (TADF)-active (ΔEST ≈0.12 eV), while the monomer (CzBP) (ΔEST ≈0.39 eV) does not. The present study examines the effect of chemical tailoring on the optical and photophysical properties of CzBP using DFT and TDDFT methods. The introduction of a single -NO2 group or di-substitution (-NO2 , -COOH or -CN) in the selected LUMO region of the reference CzBP monomer significantly reduces ΔEST ≈0.01 eV, projecting these systems as potential TADF-active emitters. Furthermore, the chemical modification of CzBP-LUMO alters the two-step TADF mechanism (T1 →T2 →S1 ) in CzBP (ES1 >ET2 >ET1 ) to the Direct Singlet Harvesting (T1 →S1 ) mechanism (ET2 >ES1 >ET1 ), which has recently been identified in the fourth-generation OLED materials.

Clinical Trajectories in Adolescents with and without a History of Non-Suicidal Self-Injury: The BRIDGES Longitudinal Study.

Background: Non-suicidal self-injury (NSSI) is a highly prevalent clinical concern in adolescents and is associated with impaired functioning and suicide risk. The BRIDGES (BRain Imaging Development of Girls' Emotion and Self) study was designed to collect longitudinal clinical and neurobiological data to advance our understanding of NSSI in adolescents. The purpose of this paper is to describe the clinical data collected as part of this study, including psychiatric diagnoses, depression symptoms, episodes of non-suicidal self-injury, suicidal thoughts and behaviors, childhood trauma, and personality domains. Methods: The baseline sample included 164 adolescents aged 12-16 assigned female at birth (Mean age = 14.97, SD = 1.20) with NSSI histories ranging from none to severe. Participants and their parent/guardian were invited to provide data at three time points spaced approximately one year apart. Descriptive analyses were conducted to provide estimates of rates and trajectories of clinical data. Results: Of the 164 study participants, 75.61% and 57.93% completed the second and third time points, respectively. Visual inspection of the data suggests an overall trend of decreasing severity of psychopathology over time, and adolescents with a history of NSSI appeared to have higher rates of psychopathology than those without. Conclusions: This paper describes longitudinal clinical trajectories in adolescents with a range of NSSI histories and presents readers with an overview of the rich, publicly available dataset that we hope will inspire future research to advance the understanding of the neurodevelopmental trajectories associated with NSSI, depression, and suicide risk.

Case report on combined approach for delayed orbital floor repair.

"White-eyed blowout" fractures in pediatric patients can be presented with fewer clinical symptoms; therefore, immediate diagnosis and surgery is essential. In cases where early surgery was performed, rapid recovery and better postoperative outcomes were noted regardless of the configuration of fracture. In pediatric patients, due to changes in the orbital volume, autograft is recommended. Although there are different approaches to orbital floor, transantral approach provides enhanced illumination and accessibility to orbital floor. This case report portrays a pediatric case of white-eyed blow out fracture which went unnoticed for about 1 month and was managed at a later date. Combined mid-tarsal and transantral approaches using iliac crest graft was used to repair the orbital blow-out fracture.

Multifaceted folding-unfolding landscape of the TrpZip2 ß-hairpin and the role of external sub-piconewton mechanical tensions.

Proteins can experience uneven tensions of the order of tens of piconewtons when exposed to different solvent environment due to the thermal motion of the solvent. It is also true that biomolecules, especially proteins, are subjected to a variety of mechanical tensions generated by several factors, including mechanically assisted translocation and pressure gradients within living systems. Here, we use metadynamics simulations to revisit the folding-unfolding of the TrpZip2 ß-hairpin and redefine it from the perspective of an external force of a sub-piconewton magnitude acting on the ends of the hairpin. The chosen forces, while preserving the morphology of the ß-hairpin chain when it is pulled, are capable of influencing the conformational behavior of the chain during folding and unfolding. Our investigations confirm that the TrpZip2 ß-hairpin exhibits a zipper (zip-out) mechanism for folding-unfolding in both mechanically unbiased and biased (with a 30 pN end force) situations. However, it is important to note that they present marked differences in their folding and unfolding paths, with the mechanically biased system capable of becoming trapped in various intermediate states. Both unbiased and biased scenarios of the hairpin indicate that the hairpin turn is highly stable during the folding-unfolding event and initiates folding. More importantly we confirm that the existing heterogeneity in the TrpZip2 ß-hairpin folding-unfolding is a consequence of the wide range of conformations observed, owing to the different trapped intermediates caused by the uneven forces it may experience in solution.

Demographics, Clinicopathological Profile of Oral Lichen Planus of South Kerala Population: A Cross-Sectional Study.

BACKGROUND:  Oral lichen planus (OLP) is a chronic mucocutaneous inflammatory lesion of unknown cause. The buccal mucosa is the most frequently affected anatomic site and the lesion is bilateral. The objective of this retrospective study was to investigate the epidemiological and clinical characteristics of 250 OLP patients in South Kerala. This was done by figuring out these patients' epidemiological and clinical characteristics. Materials and methods: In the present study, patients who reported between September 2018 and December 2021 were selected employing the diagnostic criteria consistent with the WHO classification of OLP. Data of all the patient's characteristic features were collected and evaluated using the Statistical Package for the Social Sciences (SPSS) software for statistical analysis. RESULTS:  Out of 250 patients, 52% were females and 48% were males. Reticular (n = 145, 58%) and erosive forms (n = 105, 42%) were the two clinical presentations of the lesions that were most consistently observed. The age group of 25-34 years reported the highest number of cases (n = 71, 28.4%). According to the chi-square test, there were statistically highly significant differences between the hyperpigmentation, age, and type of OLP. While 43.2% (n = 108) of cases reported a burning sensation, pain, or soreness, 56.8% (n = 142) of cases were asymptomatic. There were statistically significant differences between the type of OLP and the reported symptoms (p = 0.001). Mild to moderate dysplastic changes were documented in 5.6% during the follow-up period. A successful treatment outcome with topical steroid administration was recorded in the study sample. CONCLUSION:  It was apparent that patients typically have bilateral lesions involving the buccal and labial mucosa, manifesting with varying degrees of oral discomfort. Although patients frequently have more than one variant of OLP, the lesions are typically reticular or erosive in nature. A meticulous follow-up is crucial to determine its malignant change.

PCR-based Evaluation of Human Papillomavirus Genotypes in Oral Lichen Planus.

Objective: The objective of the study was to use polymerase chain reaction (PCR) to examine and compare the genotype distribution of human papillomavirus (HPV) in oral lichen planus (OLP). Materials and Methods: Deoxyribonucleic acid (DNA) was extracted from 20 OLP biopsy specimens. Conventional PCR assay employing consensus HPV primers was used to identify HPV DNA. Positive PCR samples were then subjected to PCR assay with HPV type-specific primers. Results: Out of the total 20 OLP specimens evaluated, eight samples (40%) were positive for HPV. Females had a 41.7% higher HPV-positive rate than males. The most common type in the HPV type-specific PCR assay was HPV-18 (75%), which is a high-risk type of HPV linked to malignant diseases. The erosive kind of OLP had the greatest percentage of HPV positives (50%). Conclusion: The present study confirms the detection of HPV in OLP lesions, as determined by PCR-coupled HPV gene sequencing, as well as its likely mechanism of malignant transformation.

Comparison of Diagnostic Ability of Conventional Film and Storage Phosphor Plate in Detecting Proximal Caries with Direct Measurements by Stereomicroscope: A Diagnostic Test Evaluation.

Background: Radiography plays an important role in detection of interproximal caries. The aim of study is to compare diagnostic ability of conventional film and photostimulable phosphor (PSP) with direct measurement using stereomicroscope in detecting proximal caries. Methodology: In this descriptive study - diagnostic test evaluation, 200 proximal surfaces of 100 extracted human posterior teeth were radiographed with dental X-ray unit. Evaluation of conventional and digital radiographs was performed twice by three observers. Carious lesions were classified based on a four-point scale (R0-R3) suggested by Abesi et al. Weighted kappa coefficients were calculated to assess intra- and interobserver agreement for each image set. Indices of diagnostic ability calculation were based on the first readings of the three observers. The scores were compared with the histological gold standard using receiver operating characteristic (ROC) analysis to evaluate diagnostic ability. Results: Intraobserver kappa coefficients calculated for each observer for each method of detecting caries ranged from 0.914 to 0.956. Interobserver kappa coefficients for each image set ranged from 0.8788 to 0.9583. The sensitivity and specificity of film for the first observer were 77.5% and 78.3% and for PSP were 77.5% and 80%, respectively. ROC analysis revealed that there were no statistically significant results (P > 0.05) between Az values for the two detection methods. Conclusion: PSP plate should be preferred over conventional films in detecting cavitated proximal caries. Further studies with more noncavitated proximal surfaces are required to conclusively establish the diagnostic ability of PSP over conventional film.

Disulfide Isomerization in nDsbD-DsbC Complex - Exploring an Internal Nucleophile Mediated Reaction Pathway.

The disulfide bond redox chemistry of proteins is believed to be mostly governed by the proton motive force. The nucleophilic and α-elimination mechanisms are also found to supplement the formation and scission of the S-S bonds. On these grounds, the possibility for an internal nucleophile assisted disulfide bond formation in the nDsbD-DsbC complex was proposed way back. Using QM/MM MD metadynamics simulations, we explore the feasibility of the proposed mechanism. Our simulations highlight the formation of the internal nucleophile Tyr42 O- and Tyr40 O- which further generates Cys103 S- necessary for the disulfide bond formation in nDsbD. Our results illustrate how the isomerase DsbC is functionally activated by nDsbD in gram-negative bacteria. Also, we foresee that the results will be important for modelling anti-bacterial compounds based on nDsbD.

Towards solvent regulated self-activation of N-terminal disulfide bond oxidoreductase-D.

N-terminal disulfide bond oxidoreductase-D (nDsbD), an essential redox enzyme in Gram-negative bacteria, consists of a single disulfide bond (Cys103-Cys109) in its active site. The enzymatic functions are believed to be regulated by an electron transfer mediated redox switching of the disulfide bond, which is vital in controlling bacterial virulence factors. In light of the disulfide bond's inclination towards nucleophilic cleavage, it is also plausible that an internal nucleophile could second the existing electron transfer mechanism in nDsbD. Using QM/MM MD metadynamics simulations, we explore different possibilities of generating an internal nucleophile near the nDsbD active site, which could serve as a fail-over mechanism in cleaving the disulfide bond. The simulations show the formation of the internal nucleophile Tyr42O- (F ≈ 9 kcal mol-1) and its stabilization through the solvent medium. The static gas-phase calculations show that Tyr42O- could be a potential nucleophile for cleaving the S-S bond. Most strikingly, it is also seen that Tyr42O- and Asp68OH communicate with each other through a proton-hole like water wire (F ≈ 12 kcal mol-1), thus modulating the nucleophile formation. Accordingly, we propose the role of a solvent in regulating the internal nucleophilic reactions and the subsequent self-activation of nDsbD. We believe that this could be deterministic while designing enzyme-targeted inhibitor compounds.

An Appraisal of Bacteriophage Isolation Techniques from Environment.

Researchers have recently renewed interest in bacteriophages. Being valuable models for the study of eukaryotic viruses, and more importantly, natural killers of bacteria, bacteriophages are being tapped for their potential role in multiple applications. Bacteriophages are also being increasingly sought for bacteriophage therapy due to rising antimicrobial resistance among pathogens. Reports show that there is an increasing trend in therapeutic application of natural bacteriophages, genetically engineered bacteriophages, and bacteriophage-encoded products as antimicrobial agents. In view of these applications, the isolation and characterization of bacteriophages from the environment has caught attention. In this review, various methods for isolation of bacteriophages from environmental sources like water, soil, and air are comprehensively described. The review also draws attention towards a handful on-field bacteriophage isolation techniques and the need for their further rapid development.

Characterization of a novel, biofilm dispersing, lytic bacteriophage against drug-resistant Enterobacter cloacae.

AIM: To characterize a novel bacteriophage, En5822, isolated from the environment against Enterobacter cloacae and exploring its application as an alternate antimicrobial. METHODS AND RESULTS: Bacteriophage was isolated from sewage sample by membrane-filtration immobilization technique. It was purified and studied for its various physical properties like microscopic structure, thermal and pH stability, latent period and burst time, antimicrobial and anti-biofilm activity as well as molecular aspects by genome sequencing and analysis. En5822 is a myovirus with relative pH and thermal stability. En5822 shows a notable reduction of host bacterial biofilm as well as planktonic cultures. Whole genome sequence analysis revealed that the En5822 genome does not contain undesirable temperate lifestyle genes, antibiotic resistance genes and toxin-encoding genes. CONCLUSIONS: En5822 displays high lytic activity, specificity and biofilm reduction capability. It has a short latent period and high burst size that aid faster activity. Its genomic and physical attributes offer possibilities for its as an alternative antimicrobial for the treatment of drug-resistant E. cloacae infections. SIGNIFICANCE AND IMPACT OF STUDY: The study describes a novel, naturally virulent bacteriophage from environment capable of lysing multi-drug resistant E. cloacae effectively. The phage could potentially serve as an alternative strategy for treating antibiotic-resistant infections.

Role of Human Papilloma Virus in Malignant Transformation of Oral Lichen Planus: A Systematic Review.

Lichen planus (LP) is a chronic inflammatory mucocutaneous disease. The disease has a cell-mediated immune reaction which is precipitated by a specific trigger which turns the self-peptides antigenic. The role of human papillomavirus (HPV) in the malignant transformation of oral LP (OLP) has always been debated. Establishing a definitive part played by HPV in the malignant transformation of OLP, would possibly provide screening for the viruses, HPV vaccination, and antiviral therapy along with conventional treatment in LP which could improve prognosis. This systematic review is to assess the role of HPV in the malignant transformation of OLP. We performed a systematic search of PubMed, MEDLINE, and Google. The information was extracted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. All full-text papers that assessed the association of HPV in malignant transformation of OLP were considered eligible. The outcome parameter included the malignant transformation of OLP. We found a total of 19 studies from which five were found suitable for the review. Results from this systematic review showed HPV is associated with OLP. There is an increased prevalence of HPV in the erosive-atrophic (EA) variant of OLP compared to non-EA variant. There seems to be no strong evidence to prove the association between HPV and malignant transformation of OLP. Taking up the oncogenic potential of high-risk types and OLP as a potentially malignant disorder, more number of studies need to be performed on the dysplastic subtype of OLP and in those OLP lesions that progress to oral squamous cell carcinomas.

Comparative Evaluation of Salivary Visfatin Levels in Healthy and Periodontally Diseased Patients before and after Scaling and Root Planing.

AIM: The aim of this study was to compare the levels of salivary visfatin in healthy controls, patients with gingivitis and patients with chronic periodontitis and also to assess the outcome of scaling and root planing (SRP) on the levels of salivary visfatin in patients with gingivitis and chronic periodontitis. MATERIALS AND METHODS: A total of 48 patients, both males and females, in the age group of 25-50 years were enrolled into three groups, based on their clinical parameters: Group I (Healthy controls - 16), Group II (Patients with gingivitis - 16), and Group III (Patients with chronic periodontitis - 16). Groups II and III were examined 2 months after SRP. The clinical parameters that were recorded include plaque index, modified gingival index, gingival bleeding index, pocket depth, and clinical attachment level. The samples of saliva were collected from each patient and the levels of visfatin were evaluated using enzyme-linked immunosorbent assay kit. RESULTS: The mean concentration of salivary visfatin at baseline was found to be highest in Group III and lowest in Group I. A statistically significant reduction (P < 0.01) in the mean concentration of salivary visfatin and the clinical parameters were observed after 2 months of SRP. CONCLUSION: The levels of salivary visfatin can thus be considered as an inflammatory biomarker for periodontal diseases. However, future longitudinal prospective studies are needed to support these findings.

Novel coronavirus- A comprehensive review.

Recently coronavirus outbreak which started in Wuhan, China, has caused international concern that has affected more than 29 lakh people worldwide and with no vaccine or specific antiviral drugs present as well as oblivious testing of carriers who are generally asymptomatic, the use of general health intervention techniques are failing to comply. As compared to other epidemics like severe acute respiratory syndrome-coronavirus (SARS-CoV) and the Middle-East respiratory syndrome (MERS-CoV), coronavirus (also named as COVID-19) exhibit mild symptoms in the majority of cases. But in the case of a vulnerable population, it can prove to be life-threatening. Relying on proper barrier technique, use of chest computed tomography scans, managing co-morbid conditions of susceptible patients, identifying the pattern of disease spread as well as the use of polymerase chain reaction to assess the specificity of cases will eventually prove to be efficacious since most of the positive cases are asymptomatic at the beginning which poses a challenge to the primary health care physicians. The development of vaccines will also take some time so it is better to know about COVID-19 better and also follow quarantine restrictions properly till then. In this review, we try to put forward all the relevant studies which have been published by the end of March 2020 so as to summarize the natural history, diagnosis as well as treatment strategies for eradicating COVID-19, which will help in managing this pandemic.